• Nutrition Research and Practice
• /
• 제4권5호
• /
• pp.369-374
• /
• 2010

Grape is one of the most popular and widely cultivated fruits in the world. Although grape skin and seeds are waste product of the winery and grape juice industry, these wastes contain large amounts of phytochemicals such as flavonoids, phenolic acids, and anthocyanidins, which play an important role as chemopreventive and anticancer agents. We evaluated efficacies of grape skin and seeds on hepatic injury induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN significantly increased levels of serum alanine transaminase, aspartate transaminase, alkaline phosphatase, and bilirubin. Diet supplementation with grape skin or seeds (10% daily for 4 weeks) prevented these elevations. The grape skin and seeds also restored serum albumin and total protein levels, and reduced the hepatic level of hydroxyproline and malondialdehyde. Furthermore, grape skin and seeds reduced DMN-induced collagen accumulation, as estimated by histological analysis of liver tissue stained with Sirius red. Grape skin and seeds also reduced hepatic stellate cell activation, as assessed by ${\alpha}$-smooth muscle actin staining. In conclusion, grape skin and seeds exhibited in vivo hepatoprotective and antifibrogenic effects against DMN-induced liver injury, suggesting that grape skin and seeds may be useful in preventing the development of hepatic fibrosis.

• 약학회지
• /
• 제41권5호
• /
• pp.622-628
• /
• 1997

Hepatic cirrhosis is a common response to chronic liver injury from many causes and is one of the most common cause of all deaths. This study was carried out to compare experimental hepatic cirrhosis in rats to understand this disease and to apply for the pharmacokinetics in disease state. Following three kinds of experimental models were induced; 1) Bile duct ligation/scission (BDL/S), 2) N, N-dimethylnitrosamine(DMN), 3) Carbon tetrachloride. The hepatic cirrhosis was characterized by examing the liver/body weight ratio, serum biochemical values, hydroxyproline content in liver and histopathological lesions in cirrhotic rat liver. The results are as follows : (1) In BDL/S, the liver was enlarged to 250% of normal liver. In contrast the liver was shrinked to 48% and 78% of the normal liver in DMN and carbon tetrachloride, respectively. (2) In carbon tetrachloride and BDL/S, the serum ALT, AST, ALP and total bilirubin levels were significantly increased to 200~300% of normal level, while ALT and total bilirubin levels were significantly increased in DMN group. (3) Hydroxyproline content in cirrhotic rat liver was significantly 200~500% higher than that of normal liver. (4) Nodular formation with fibrosis was observed in BDL/S, DMN, carbon tetrachloride induced cirrhotic rat liver.

• Journal of Yeungnam Medical Science
• /
• 제4권1호
• /
• pp.89-96
• /
• 1987

동물의 간소엽에 심한 지방성병변과 괴사성병변을 일으키는 사염화탄소와 이와 비슷한 독작용을 가지고 동물의 간소엽에 심한 출혈성 괴사성병변을 초래하는 Dimethylnitrosamine이 동일물질의 2~3회 반복투여에 의해서 어떠한 영향을 받는가를 비교, 관찰하기 위하여 체중 150~200gm의 백서를 실험동물로 사용하여 Sublethal dose의 사염화탄소(0.4ml/kg)와 DMN(40mg/kg)을 1회, 2회 및 3회 복강내로 주입하여 간소엽에 나타난 병리조직학적 병변을 요약하면 다음과 같다. 1. 사염화탄소를 1회 투여한 동물의 간소엽에 있어서 지방변성 괴사성병변에 비해 2회 또는 3회 반복투여한 동물의 병변정도가 경하였고, 또 간세포나 동양세포의 재생성 변화도 더 빨리 일어났다. 2. DMN을 1회 투여한 동물에 있어서의 괴사성병변은 2회 또는 3회 투여한 군의 그것과 큰 차이는 없었지만 간세포의 증식성 변화는 DMN의 투여회수가 많을수록 비례해서 강하게 나타나는 경향을 보였다.

• Parasites, Hosts and Diseases
• /
• 제46권3호
• /
• pp.127-132
• /
• 2008

Clonorchis sinensis is one of the most prevalent parasitic helminths in Korea. Although cholangiocarcinoma can be induced by C. sinensis infection, the underlying mechanism is not clearly understood. To assess the role of C. sinensis infection in carcinogenesis, an in vitro system was established using the human epithelial cell line HEK293T. In cells exposed to the excretory/secretory products (ESP) of C. sinensis and the carcinogen dimethylnitrosamine (DMN), cellular proliferation and the proportion of cells in the G2/M phase increased. Moreover, the expression of the cell cycle proteins E2F1, p-pRb, and cyclin B was dramatically increased when ESP and DMN were added together. Similarly, the transcription factor E2F1 showed its highest level of activity when ESP and DMN were added simultaneously. These findings indicate that DMN and ESP synergistically affect the regulation of cell cycle-related proteins. Our results suggest that exposure to C. sinensis and a small amount of a carcinogen such as DMN can promote carcinogenesis in the bile duct epithelium via uncontrolled cellular proliferation and the upregulation of cell cycle-related proteins.

• 산업융합연구
• /
• 제19권6호
• /
• pp.177-186
• /
• 2021

본고는 인지적 과제를 수행하는 동안 우울 및 불안 환자의 정신병리적 과정과 이의 치료접근 방식에 대한 통합적 이해를 위해 최근 제시된 신경인지 연결망을 토대로 인지과정 및 정서조절의 비정상적 기능 연결성을 재해석 할 수 있는 모델을 제안하고자 하였다. 재구성된 우울과 불안장애 신경인지 연결망 모델을 통해, 우울증은 불이행방식 연결망(default mode network; DMN)의 과다 활성화에 기인하는 '자기참조적 사고로의 과몰입'으로, 불안장애는 불이행방식 연결망의 과소 활성화에 기인하는 '자기참조적 사고와의 단절'로 규정해 볼 수 있음을 확인하였다. 신경인지 연결망 중 자기의식 및 투사와 관련되는 자기참조 처리가 주요 기능인 DMN의 비정상적 활성화와 병리적 기능의 체계적 연결시도는 우울와 불안에 대한 통합적 해석과 치료적 접근에 시사점을 줄 수 있는 또 다른 출발점이 될 수 있을 것이다.

• Biomaterials and Biomechanics in Bioengineering
• /
• 제1권2호
• /
• pp.73-79
• /
• 2014

Covalent attachment of 1, 4-dimethylnaphthalene (DMN) based endoperoxide forming subunits to a polyvinyl butyral (PVB) backbone has been achieved. The functionalized polymer materials prepared and characterized here can serve as biocompatible carrier systems for studying cellular uptake, intermediate storage and delayed release of singlet oxygen, which opens up new doors for optimizing a variety of medical applications of photogenerated DMN-endoperoxides such as antiviral, antibacterial, antiplasmodial and antitumor activity.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.122.1-122.1
• /
• 2003

Morin, one of the major natural flavonoids has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the hepatoprotective effect of morin on the dimethylnitrosamine (DMN)-induced liver damage in rats. Oral administration of morin (10, 20mg/kg daily for 4 weeks) into the DMN-treated rats remarkably prevented the elevation of serum alanine transaminase, aspartate transaminase and alkaline phospatase, and bilirubin levels. Morin also increased serum protein level and reduced the hepatic level of malondialdehyde in DMN-treated rats. (omitted)

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.116.2-116.2
• /
• 2003

Aspirin and aspirin-like nonsteroidal antiinflammatory drug have been the mainstay of therapy for rheumatoid arthritis. In this study, we investigated the hepatoprotective effect of aspirin on the dimethylnitrosamine (DMN)-induced liver damage in rats. Oral administration of aspirin (7.5, 15mg/kg daily for 4 weeks) into the DMN-treated rats remarkably prevented the elevation of serum alanine transaminase, aspartate transaminase and alkaline phosphatase, and bilirubin levels. Aspirin also increased serum protein level and reduced the hepatic level of malondialdehyde in DMN-treated rats. (omitted)

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.289.1-289.1
• /
• 2002

Quercetin, one of the most abundant flavonoids in human diet has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the protective effect of quercetin on hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN caused a significant decrease in body and liver weight. Oral administration of quercetin (10 mg/kg daily for 4 weeks) remarkably prevented this DMN-induced loss in body and liver weight and inhibited the elevation of serum alanine transaminase. aspartate transaminase, and bilirubin levels. (omitted)

• Archives of Pharmacal Research
• /
• 제25권5호
• /
• pp.655-663
• /
• 2002

Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDb) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, po, 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, po, 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.